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Progressive Multifocal Leukoencephalopathy (PML)

By

John E. Greenlee

, MD, University of Utah School of Medicine

Last full review/revision Jul 2020| Content last modified Jul 2020
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Progressive multifocal leukoencephalopathy is a rare infection of the brain that is caused by the JC (John Cunningham) virus.

  • People with a weakened immune system are most likely to get the disorder.

  • People may become clumsy, have trouble speaking, and become partially blind, and mental function declines rapidly.

  • Death usually occurs within 9 months.

  • Imaging of the head and a spinal tap are done.

  • Treating the disorder that weakened the immune system may help people live longer.

Progressive multifocal leukoencephalopathy results from infection by the JC virus. The JC virus is often acquired during childhood. Most adults have been infected with the JC virus but do not develop the disorder.

The virus appears to remain inactive until something (such as a weakened immune system) allows it to be reactivated and start to multiply. Thus, the disorder affects mainly people whose immune system has been weakened by a disorder (such as leukemia, lymphoma, or AIDS) or by drugs that suppress the immune system (Immunosuppressants) or that modify the immune system (immunomodulators). Such drugs include those used to prevent rejection of transplanted organs or to treat cancer or autoimmune disorders, such as systemic lupus erythematosus (lupus) or multiple sclerosis. These drugs include natalizumab and rituximab, which are monoclonal antibodies, and brentuximab vedotin, which is an anticancer drug combined with a specific antibody that targets cancer cells.

Symptoms

The JC virus appears to cause no symptoms until it is reactivated.

Symptoms of progressive multifocal leukoencephalopathy may begin gradually and usually worsen progressively. They vary depending on which part of the brain is infected.

The first symptoms may be clumsiness, weakness, or difficulty speaking or thinking. As the disorder progresses, many people develop dementia and become unable to speak. Vision may be affected. People with progressive multifocal leukoencephalopathy eventually become bedbound. Rarely, headaches and seizures occur, mainly in people with AIDS.

Death is common within 1 to 9 months of when symptoms start, but a few people survive longer (about 2 years).

People who develop progressive multifocal leukoencephalopathy while taking a drug that suppresses the immune system (such as natalizumab) may recover once the drug is stopped. However, many continue to have problems related to the infection.

Diagnosis

  • Magnetic resonance imaging

  • A spinal tap

Unexplained, progressively worsening symptoms in people with a weakened immune system suggest progressive multifocal leukoencephalopathy.

Magnetic resonance imaging (MRI) of the head is done. It can usually detect abnormalities that suggest the diagnosis.

A spinal tap (lumbar puncture) is done to obtain a sample of cerebrospinal fluid (the fluid that flows through the tissues that cover the brain and spinal cord). The polymerase chain reaction (PCR) technique, which produces many copies of a gene, is used to detect the JC virus's DNA in the cerebrospinal fluid.

Treatment

  • If the cause is a weakened immune system, treatment of the cause

No treatment for progressive multifocal leukoencephalopathy has proved effective. However, if the disorder that has weakened the immune system is treated, people survive longer. For example, if the cause is AIDS, antiretroviral therapy is used.

If people are taking immunosuppressants or other drugs that affect the immune system (such as natalizumab), stopping the drugs may cause progressive multifocal leukoencephalopathy to subside. Then plasma exchange is used to remove the drug from the blood, particularly when the drug is natalizumab (used to treat multiple sclerosis).

People who are treated with antiretroviral therapy or who stop taking immunosuppressants may develop immune reconstitution inflammatory syndrome (IRIS). In this disorder, the recovering immune system launches an intense attack against the JC virus, which can make symptoms temporarily worse. Corticosteroids may help relieve symptoms.

NOTE: This is the Consumer Version. DOCTORS: Click here for the Professional Version
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